Mechanistic Analysis of Intramolecular Free Radical Reactions toward Synthesis of 7-Azabicyclo[2.2.1]heptane Derivatives

Abstract

The mechanisms for the formation of conformationally constrained epibatidine analogues by intramolecular free radical processes have been computationally addressed by means of DFT methods. The mechanism and the critical effect of the 7-nitrogen protecting group on the outcome of these radical-mediated cyclizations are discussed. Theoretical findings account for unexpected experimental results and can assist in the selection of proper precursors for a successful cyclization.

Chemoenzymatic enantioselective synthesis of 7-azabicyclo[2.2.1]heptane derivatives

“…24,25 Due to the importance of these compounds, there has been considerable interest in the design of efficient methods for their synthesis. [26][27][28][29][30][31][32][33] Enzymatic desymmetrization of prochiral or meso compounds to yield enantiomerically enriched products has proved to be a valuable tool in asymmetric synthesis. [34][35][36] In contrast to the classic kinetic resolution of racemic mixtures, the theoretical maximum yield of these transformations is 100%.…”

Formation of Five- and Six-Membered Heterocyclic Rings under Radical Cyclization Conditions

“…Soriano and Marco-Contelles studied 63 the mechanism of formation of conformationally constrained epibatidine analogues by intramolecular free-radical cyclization by means of DFT methods. Theoretical findings account for the unexpected experimental results and may assist in the selection of proper precursors for a successful reaction.…”